Cardiomyocytes
About Cardiomyocytes
Cardiomyocytes (myocytes) measure up to 25 um in diameter and 100 um in length.
They are arranged in a circumferential and spiral orientation around the left ventricle.
Each cell contains numerous myofibrils, which are long chains of sarcomeres. Sarcomeres are the fundamental contractile unit of the cell, being made up of actin and myosin.
Within each cardiomyocyte sarcomeres line up, producing the characteristic cross-striated banding pattern.
The cell membrane is termed to sarcolemma. Deep invaginations of the sarcolemma called T tubules project into the cell, increasing contact with the extracellular environment and facilitating rapid conduction of calcium influx and contractility. Gap junctions between cells are termed intercalated disks and stain darkly on light microscopy.
Most calcium is stored with the sarcoplasmic reticulum.
Given their tremendous energy demands, cardiomyocyte volume is approximately 35% mitochondria, located between individual myofibrils.
Depolarization
Unlike the pacemaker cells of the heart, cardiomyocytes do not spontaneously depolarize. Instead, they rely on signals from the electrical components of the heart - the SA node, AV node, bundle of His, and Purkinje fibres.
Phase 0
Once depolarization signals arrive at cardiomyocytes, sodium channels open. Once threshold is reached (-70 mV), a self-sustaining Na inward current carries the cell to 0 mV and transiently into the positive range.
Rapid inactivation of Na channels makes this short-lived. Calcium L-type channels open at -40mV and remain open for a much longer period, providing the signal for contraction.
Phase 1
Following depolarization, transiently opened potassium channels return the membrane potential to 0 mV.
Phase 2
An outward K+ current is balanced by the still-happening inward Ca2+ current, leading to the plateau.
Phase 3
The gradual inactivation Ca2+ channels, and the continued outward K+ current, returns the membrane potential to -90 mV.
A long refractory period allows ventricles sufficient time to eject blood and refill before the next contraction.
The degree of refraction depends on the number of inactivated sodium channels. The absolute refractory period is followed by the relative refractory period, during which greater than normal stimulation is required to depolarize the cell. The atrial refractory period is generally shorter than that of ventricular cells, such that atrial rates can exceed those of the ventricles during arrhythmias.
Phase 4
Open K+ channels keep cardiomyocytes stable at -90 mV, as predicted by the Nerst Equation. The cell is thus ready for the next round of depolarization.
To maintain ion gradients, various pumps remove ions to the extracellular space and return calcium to the sarcolemma.
Contraction
To Do: actin, myosin, tropomyosin, troponin.
Calcium entry from the extracellular space is insufficient to cause myofibril contraction. Instead, L-type channels are in close opposition to ryanodine receptors on the sarcoplasmic reticulum. Calcium binding to these receptors results in massive release of calcium stored in the sarcoplasmic reticulum - the calcium-induced calcium release (CICR).
Calcium ions bind to Troponin C, inhibiting TnI and leading to a conformational change in tropomyosin. This exposes the active site between actin and myosin, and contraction occurs.
Talk about ATP...
With the inactivation of L-type channels, calcium influx falls and calcium is pumped back into the SR and out if the cell.
Control of Contractility
The concentration of intracellular calcium is the major determinant of the force of cardiac contractility.
Beta-adrenergic stimulation activates the G protein system, which in turn stimulates adenylate cyclase and the production of cAMP. This leads to phosphorylation pathways which increase L-type channel influx and SR release.
Beta-adrenergic stimulation also increases cardiomyocyte relaxation via phospholamban.